Most instances of social interaction provide a wealth of information about the states of other people, be it sensations, feelings, thoughts, or convictions. How we represent these states has been a major question in social neuroscience, leading to the identification of two routes to understanding others: an affective route for the direct sharing of others’ emotions (empathy) that involves, among others, anterior insula and middle anterior cingulate cortex and a cognitive route for representing and reasoning about others’ states (Theory of Mind) that entails, among others, ventral temporoparietal junction and anterior and posterior midline regions. Additionally, research has revealed a number of situational and personal factors that shape the functioning of empathy and Theory of Mind. Concerning situational modulators, it has been shown, for instance, that ingroup membership enhances empathic responding and that Theory of Mind performance seems to be susceptible to stress. Personal modulators include psychopathological conditions, for which alterations in empathy and mentalizing have consistently been demonstrated; people on the autism spectrum, for instance, are impaired specifically in mentalizing, while spontaneous empathic responding seems selectively reduced in psychopathy. Given the multifaceted evidence for separability of the two routes, current research endeavors aiming at fostering interpersonal cooperation explore the differential malleability of affective and cognitive understanding of others.